Enhancing cognitive memory function using Phyllanthus emblica polysaccharides via modulating autophagy and reshaping...

Area of Science:

• Neuroscience
• Pharmacology
• Microbiology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuroinflammation, oxidative stress, amyloid-beta (Aβ) plaques, Tau hyperphosphorylation, and gut dysbiosis.
• Natural polysaccharides may mitigate cognitive decline by modulating the microbiota-gut-brain axis, enhancing autophagy, and clearing AD-related proteins.
• Phyllanthus emblica polysaccharides (PEP) possess known anti-inflammatory, antioxidant, and gut microbiota-modulating effects, but their role in AD prevention requires investigation.

Purpose of the Study:

• To investigate the potential of Phyllanthus emblica polysaccharides (PEP) in preventing Alzheimer's disease (AD).
• To elucidate the underlying mechanisms of PEP's preventive effects against AD pathology and cognitive impairment.

Main Methods:

• Physicochemical characterization of PEP (MW: 1.182 × 10³ kDa) as a heat-stable α-acidic pyran heteropolysaccharide.
• In vivo study using AlCl₃-treated rats to assess cognitive function, neuroinflammation, oxidative stress, and AD-related protein levels.
• Analysis of autophagy-related proteins, LRP1, BACE1, APP, Aβ, and Tau phosphorylation.
• Gut microbiota analysis, focusing on short-chain fatty acids (SCFAs) and specific bacterial groups.

Main Results:

• PEP administration significantly alleviated cognitive decline in AlCl₃-treated rats.
• PEP reduced neuroinflammatory cytokines (TNF-α, IL-6, IL-1β) and MDA levels, while increasing anti-inflammatory factors (IL-4, IL-10) and antioxidants (SOD, catalase, GPx).
• PEP upregulated autophagy proteins (Atg5, Beclin1, LC3B) and LRP1, and downregulated AD markers (BACE1, APP, Aβ, phospho-Tau^Ser404).
• PEP treatment increased SCFAs and SCFA-producing bacteria, notably Christensenellaceae_R-7_group.

Conclusions:

• PEP demonstrates significant preventive effects against AlCl₃-induced cognitive impairment in rats.
• PEP exerts its protective effects through antioxidant, anti-inflammatory, autophagy-inducing, and AD-related protein-suppressing mechanisms.
• PEP positively modulates the gut microbiota composition and SCFA production, contributing to its neuroprotective benefits.